Anthropometric traits and risk of multiple myeloma: differences by race, sex and diagnostic clinical features.

BACKGROUND: Obesity is an established modifiable risk factor for multiple myeloma (MM). However, associations of obesity and MM risk in Black populations, for whom obesity and MM are more common, is less clear. METHODS: Using participants enrolled in the Integrative Molecular And Genetic Epidemiology study, we evaluated the association of anthropometric traits with MM risk overall, stratified by race and sex. Among cases, we assessed the association of BMI with the presence of myeloma-defining events. RESULTS: We observed an 18% increase in MM risk for every 5 kg/m2 increase in usual adult BMI. Participants with severe obesity (BMI ≥ 40 kg/m2) had the highest risk compared to those with a normal usual adult BMI (18.5-24.9 kg/m2; OR = 1.87, 95% CI 1.25-2.80), particularly among Black men (OR = 3.94, 95% CI 0.90-17.36). Furthermore, MM cases with overweight/obesity (BMI ≥ 25 kg/m2) were more likely to present at diagnosis with low renal function (OR = 1.62, 95% CI 1.09-2.40), deletion 13q (OR = 1.73, 95% CI 1.08-2.76) and lytic lesions or compression fractures (OR = 2.39, 95% CI 0.82-7.01) and less likely to present with severe diffuse osteopenia (OR = 0.51, 95% CI 0.31-0.81). CONCLUSIONS: Findings underscore the importance of obesity as a modifiable risk factor for MM, particularly in high-risk populations, and for the clinical presentation of disease.

Subsequent therapy and outcomes in patients with newly diagnosed multiple myeloma experiencing disease progression after quadruplet combinations.

The combination of anti-CD38 monoclonal antibodies to a proteasome inhibitor, an immunomodulatory agent and dexamethasone (quadruplet-QUAD) in sequence with autologous stem cell transplantation (ASCT) leads to deep and durable responses in newly diagnosed multiple myeloma (NDMM). Disease progression in the first year post-QUADs is uncommon. We analysed 274 consecutive NDMM patients treated with QUADs + ASCT. After a median follow-up of 21.3 months, 20 patients had disease progression <18 months and 21 had progression ≥18 months after the onset of a QUAD regimen. All patients received subsequent anti-MM therapy, and 38 were evaluated for response. Nine (22.0%) received T-cell redirecting therapy as the next treatment, and 21 (51.2%) at some point in the treatment course. Response to next therapy was 26.3% for patients with progression <18 months and 52.6% for those with progression ≥18 months after the onset of a QUAD regimen. Median PFS on the next therapy was 2.5 months (95% CI 1.5-3.4) for those with progression <18 months and 7.0 months (95% CI 3.6-10.5) for those with progression ≥18 months. Efforts should focus on the early deployment of therapies with new mechanism of action for patients experiencing treatment failure after QUADs.

Bispecific T-cell engagers for treatment of multiple myeloma.

Bispecific T cell engagers (TCE) derive from monoclonal antibodies and concomitantly engage a target on the surface of cancer cell and CD3 on the surface of T-cells. TCEs promote T cell activation and lysis of tumor cells. Most TCEs in development for multiple myeloma (MM) target the B cell maturation antigen (BCMA) and differ among themselves in structure, pharmacokinetics, route and schedule of administration. CD3/BCMA TCEs produce response in ~60% of patients treated in phase 1 trials. TCEs are also in development targeting the G protein-coupled receptor, class C group 5 member D (GPRC5D) and the Fc receptor homologue 5 (FcRH5). Main toxicities are cytokine release syndrome and cytopenias. Here we review the current development and future directions of TCEs in MM.

Does recipient body mass index inform donor selection for allogeneic haematopoietic cell transplantation?

It is not known whether obesity has a differential effect on allogeneic haematopoietic cell transplantation outcomes with alternative donor types. We report the results of a retrospective registry study examining the effect of obesity [body mass index (BMI) > 30] on outcomes with alternative donors (haploidentical related donor with two or more mismatches and receiving post-transplant cyclophosphamide [haplo] and cord blood (CBU)] versus matched unrelated donor (MUD). Adult patients receiving haematopoietic cell transplantation for haematologic malignancy (2013-2017) (N = 16 182) using MUD (n = 11 801), haplo (n = 2894) and CBU (n = 1487) were included. The primary outcome was non-relapse mortality (NRM). The analysis demonstrated a significant, non-linear interaction between pretransplant BMI and the three donor groups for NRM: NRM risk was significantly higher with CBU compared to haplo at BMI 25-30 [hazard ratio (HR) 1.66-1.71, p < 0.05] and MUD transplants at a BMI of 25-45 (HR, 1.61-3.47, p < 0.05). The results demonstrated that NRM and survival outcomes are worse in overweight and obese transplant recipients (BMI ≥ 25) with one alternative donor type over MUD, although obesity does not appear to confer a uniform differential mortality risk with one donor type over the other. BMI may serve as a criterion for selecting a donor among the three (MUD, haplo and CBU) options, if matched sibling donor is not available.

Protamine sulfate for the reversal of enoxaparin associated hemorrhage beyond 12 h.

Clinical practice guidelines recommend protamine sulfate for reversal of enoxaparin associated bleeds dependent on the time from last administration and dose of enoxaparin. We present a case of a hemodynamically unstable patient with an enoxaparin induced abdominal wall hematoma/hemorrhage and the previous enoxaparin administration 21.5 h prior to presentation with a therapeutic anti-Xa assay (0.8 IU/mL) upon assessment in the emergency department. Along with resuscitative efforts, an interdisciplinary team collaborated to administer protamine sulfate 50 mg intravenous once (0.5 mg per 1 mg of enoxaparin) to reverse the therapeutic anticoagulation. Our case demonstrates the importance of monitoring renal function and the potential for accumulation of enoxaparin in patients with renal dysfunction leading to prolonged therapeutic anti-Xa assays. With the availability of anti-Xa assays, future reversal recommendations of enoxaparin associated bleeds using protamine sulfate should include the initial anti-Xa assay as a guide for the dosing regimen.

Hospital Associated Disability among Older Adults with Plasma Cell Disorders Receiving Autologous Stem Cell Transplant.

Increasing number of older adults with Plasma Cell Disorders (PCDs) are receiving autologous stem cell transplant (ASCT) in the US. Hospital associated disability (HAD) is a common complication associated with acute care hospitalization among older adults. To estimate the prevalence and prognostic significance of HAD among older adults with MM undergoing ASCT. This retrospective cohort study used consecutive adults ≥ 18 y with PCD receiving ASCT at a single institution between 1/2013 and 5/2023. Trained nursing staff assessed Katz Activities of Daily Living (ADL) at admission and every 3 days thereafter under our Virtual Acute Care for Elders program. The primary outcome was development of HAD defined as ≥1 point decline on the Katz Activities of Daily Living (ADL) scale from hospital admission to discharge. We examined the association between putative risk factors such as age, Karnofsky performance status (KPS), baseline ADL score, Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) and HAD using modified Poisson regression models with robust variance estimators. Subsequently, we studied the impact of HAD on downstream adverse events including 30-day readmission rates and long term survival. We included 778 adults with a median age of 62 y (QR 56-68 y), with 56% males and 55% non-Hispanic Whites. In the overall population, 112 (14.4%) developed HAD, with much higher incidence among older adults ≥ 65 y compared to those <65 y at ASCT (22% vs. 9%, P value < .01). In multivariable analysis, increasing age (RR 1.56; 95% CI 1.25-1.94, per 10 y increase), female sex (RR 1.79; 95% CI 1.27-2.53) and KPS ≤ 70 (RR 2.55; 95% CI 1.32-4.94) were associated with an increased risk of developing HAD. As compared to those without, patients with HAD had a two-fold higher risk of 30-day readmission (95% CI 1.16-3.39) and a 3.7-fold increased risk of all-cause mortality (95% CI 2.15-6.22). Nearly one in 4 older adults ≥ 65 y developed HAD while undergoing ASCT which was associated with a two-fold increased risk of 30-day readmission. Interventions to prevent HAD and its downstream consequences are critically needed.

Understanding health outcome preferences of older adults diagnosed with multiple myeloma.

INTRODUCTION: Health outcome preferences of older adults with cancer vary based on burden/intensity of treatment and its impact on health outcomes such as survival, quality of life, and functional and cognitive well-being. We studied the association between age and health outcome preferences of adults with multiple myeloma (MM). MATERIALS AND METHODS: Using a single center prospective cohort study, we identified adults ≥50y with MM who underwent geriatric assessment (GA) within 30 days of initiating a new line of therapy. We assessed health outcome preferences using a nine-item health outcome preference scale where patients were asked to prioritize varying treatment outcomes in a Likert scale. We compared the response patterns for each item by age group (50-69y vs ≥70y) using Mantel-Haenszel chi-squared test. For items significant in bi-variable analysis, we built proportional odds models to study the association between age and health outcome preferences adjusting for sex, race, frailty, and high risk cytogenetics. RESULTS: We included 119 patients with a median age of 65y. Of these, 58% were male, 56% were non-Hispanic White, and 28% were frail. Older adults (≥70y) versus younger adults (50-69y) were more likely to prioritize health outcomes such as quality of life (53% vs. 34%), functional independence (74% vs. 33%), maintaining cognitive ability (79% vs. 54%), and living free from pain (50% vs 18%) over longer survival (all p values <0.05). In multivariable models, each one interquartile range (IQR) increase in age was associated with increased odds of prioritization of functional independence [adjusted odds ratio (aOR) 2.55, 95% confidence interval (CI) (1.44-4.53)], maintaining cognitive ability [aOR 1.75, 95% CI (1.01-3.02)], and willingness to take milder/ fewer treatments [aOR 2.40, 95% CI (1.36-4.26)] over longer survival. Similarly, each IQR increase in age was associated with decreased odds of prioritization of survival over quality of life [aOR 0.45, 95% CI (0.26-0.78)] and survival over being free from pain [aOR 0.39, 95% CI (0.22-0.69)]. DISCUSSION: Three out of four older adults (age ≥ 70y) with MM rated other outcomes, particularly functional and cognitive well-being, above survival. Determining the most significant treatment outcomes for older adults with MM can aid in establishing treatment goals and enhance shared decision-making.

Evaluating concordance between International Myeloma Working Group (IMWG) frailty score and simplified frailty scale among older adults with multiple myeloma.

INTRODUCTION: Several frailty assessment tools exist for classifying older adults with multiple myeloma (MM) by their frailty status, such as the International Myeloma Working Group (IMWG) frailty score and the simplified frailty scale. The level of agreement between the IMWG frailty score and the simplified frailty scale remains unknown. MATERIALS AND METHODS: In a cross-sectional analysis of a prospective cohort study, we identified adults ≥50y initiating a new treatment regimen for MM who underwent a baseline geriatric assessment (GA). Using data from the GA and electronic health records, we measured IMWG frailty score and the simplified frailty scale, and classified patients by frailty status. We merged the fit and intermediate-fit categories of IMWG frailty score to create a binary category (frail, non-frail) for comparison with simplified frailty scale and measured their agreement using Cohen's Kappa statistic. We tested the diagnostic utility of simplified frailty scale as a screening tool using IMWG frailty score as the gold standard, using sensitivity, specificity, and decision curve analysis (DCA). RESULTS: Three hundred older adults were included with a median age at diagnosis of 64y; 56 % were male and 63 % were non-Hispanic White. By IMWG frailty score, 41 % were fit, 38 % intermediate-fit, and 21 % frail, while simplified frailty scale indicated 22 % frail and 78 % non-frail patients. The agreement between IMWG frailty score and simplified frailty scale was moderate (κ = 0.43); 19 % of the patients were misclassified. Despite discordance, when testing simplified frailty scale as a screening tool, we found a sensitivity of 56 % and specificity of 87 % to diagnose frailty. Substituting patient-reported performance status (PS) instead of physician reported ECOG PS led to a sensitivity of 91 % and specificity of 61 %. DCA showed that using simplified frailty scale (with patient reported PS) as a screening tool led to a 43-44 % reduction in the number of unnecessary GAs across reasonable threshold probabilities. DISCUSSION: IMWG frailty score and simplified frailty scale have limited agreement with each other. This creates a possibility of misclassification bias and poses difficulty in comparing existing literature on frail patients with MM. Despite discordance, simplified frailty scale may have a potential role as a screening tool, when using patient-reported PS.

Current approach to Waldenström Macroglobulinemia.

Waldenström Macroglobulinemia (WM) is a unique, low grade, IgM lymphoplasmacytic lymphoma with a heterogeneous clinical course. A paucity of high-grade evidence from large phase 3 trials remains a major issue in the field despite a rapidly expanding therapeutic armamentarium against WM. Prior knowledge of the patients' MYD88L265P and CXCR4 mutation status aids in treatment decision making if Bruton's tyrosine kinase (BTK) inhibitor therapy is being considered. Head-to head comparative data to inform optimal approach are lacking, and a particularly vexing issue for the clinicians is choosing between fixed-duration bendamustine-rituximab (BR) therapy and an indefinite BTK inhibitor-based regimen, given that both approaches are well tolerated and effective, particularly for the patient population harboring MYD88L265P mutation. For the patients with MYD88WT genotype, chemo-immunotherapy such as BR is preferred, although zanubrutinib, a potent second generation BTK inhibitor, with its reduced off target effects and greater BTK occupancy compared to its predecessor, ibrutinib, has also recently shown activity in MYD88WT WM. This review summarizes the current literature pertaining to the diagnosis, prognosis, and the treatment of WM.

History of drug use in allogeneic hematopoietic cell transplant recipients.

Allogeneic hematopoietic cell transplant (HCT) is a curative therapy for malignant and non-malignant blood diseases. Drug use may be associated with adverse outcomes. We performed a retrospective analysis to assess non-relapse mortality (NRM) and overall survival (OS) in HCT patients with drug use. The medical charts of 232 patients were reviewed. Recipients of matched unrelated donor (MUD) or matched related donor (MRD) transplants were included. Drug use was defined by either metabolic evidence or provider documentation prior to transplant. Transplants were MUD (n = 148) or MRD (n = 84). Median follow-up duration was 15.5 months. There were 35 (15%) patients in the drug use group and 197 (85%) patients in the control group; 49% and 60.4% were in remission at the time of transplant, respectively. In univariate analysis, drug use was associated with a 3-year cumulative incidence of NRM of 43% vs 29% for the control group (p = 0.048), and an HR of 1.75, (95% CI: 1.02-2.99). After controlling for age, sex, disease status, and graft type, drug use was associated with a hazard ratio (HR) of 1.6 (95% CI: 0.95-2.92) for NRM, and an HR 1.2 (95% CI: 0.74-1.94) for OS. Larger cohorts may be needed to further evaluate this association.

Physical Activity and Sleep Measures Using a Fitness Tracking Device during Hematopoietic Cell Transplantation: A Pilot Study.

Patients undergoing hematopoietic cell transplantation (HCT) experience decline in their physical activity during their transplant admission. There is limited experience with prospective monitoring of transplant recipients. We therefore measured physical activity and sleep patterns of subjects undergoing autologous and allogeneic HCT. Eighty-three patients were consented for this study. Sixty-three patients competed the study and had their physical activity prospectively assessed using the fitness-tracking device Fitbit HR. Outcomes included adherence, physical activity, readmission, hematopoietic engraftment, and 100-day survival. Sixty percent of patients (n = 37) underwent autologous HCT, and 40% (n = 26) underwent allogenic HCT. Both groups had a comparable number of steps at admission to the hospital. The number of daily steps during the study period was lower in the allogeneic group (2159 versus 3008, P = .07), as was the minimum number of steps recorded over the transplant admission (allogeneic HCT = 395 versus autologous HCT = 848, P = .01). Patients undergoing allogeneic HCT were less active on the day before discharge (1956 steps versus 3183 steps, P = .08). In multivariate analysis, physical activity was not associated with HCT-related outcomes. Patients undergoing HCT experience significant decline in their physical activity during their transplant admission that does not recover by the time of discharge. This effect can be objectively measured using fitness tracking devices.